Br Heart J 1987;58:306-15 Review Da Costa's syndrome or neurocirculatory asthenia

OGLESBY PAUL From the Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA SUMMARY The syndrome variously called Da Costa's syndrome, effort syndrome, neuro- circulatory asthenia, etc has been studied for more than 100 years by many distinguished physi- cians. Originally identified in men in wartime, it has been widely recognised as a common chronic condition in both sexes in civilian life. Although the symptoms may seem to appear after infec- tions and various physical and psychological stresses, neurocirculatory asthenia is most often encountered as a familial disorder that is unrelated to these factors, although they may aggravate an existing tendency. Respiratory complaints (including breathlessness, with and without effort, and smothering sensations) are almost universal, and palpitation, chest discomfort, dizziness and faintness, and fatigue are common. The physical examination is normal. The aetiology is obscure but patients usually have a normal life span. Reassurance and measures to improve physical fitness are helpful. Da Costa's syndrome or neurocirculatory asthenia Although Jacob M Da Costa is the name most has a long and honourable history in the medical honoured by history in this condition, at least one literature and in clinical medicine. Yet it is infre- other relevant report antedated his paper in 1871. quently mentioned today. It is unlikely to have dis- On 3 June 1863 Dr Henry Hartshorne made a appeared; it probably exists much as before but is presentation regarding heart disease in the Union more often identified and labelled in psychiatric Army to the College of Physicians in Philadelphia. terms such as "anxiety state" or "anxiety neurosis". He commented: "Among the chronic affections of There is no harm in this shift in diagnostic labels as soldiers, which are best studied in hospitals remote long as the essential importance of the syndrome, its from the field, is one which does not seem to have prognosis, and treatment are properly appreciated. met, as yet, with full appreciation by medical Such is not always the case and, as in other medical officers, inspectors and pension surgeons... The issues, it is educational to review and summarise the affection to which I allude may be designated as mus- past. What has been forgotten should not necessarily cular exhaustion of the heart."' remain forgotten. Dr Hartshome went on to mention that Dr Alfred For the purposes of this discussion, a broad Stille had delivered an address on a somewhat simi- definition of Da Costa's syndrome that is applicable lar disorder, referred to by him as "palpitation", to military and civilian patients is: a disorder of before the Philadelphia County Medical Society unknown origin, often familial, characterised by the four months earlier.2 Stille had noted that this pal- presence of one or more symptoms including pitation was "a very frequent symptom among the breathlessness with and without effort, palpitation, soldiers, occurring in perhaps every case of inter- nervousness, chest discomfort not typical of angina costal neuralgia, but often, also, originating appar- pectoris caused by ischaemic heart disease, ently in a state of extreme exhaustion..." fatigability, and faintness; tending to occur in Hartshorne described how in an 80 bed ward of a attacks which may recur over years and for which Union army hospital over a seven month period the there is no specific treatment. majority of the cardiac patients exhibited neither hypertrophy nor dilatation, or palpitation "from sympathy with irritated stomach, from nervousness, Requests for reprints to Dr Oglesby Paul, Countway Library of abuse of tobacco, etc", but cardiac muscular exhaus- Medicine, Harvard Medical School, 10 Shattuck Street, Boston, tion. This was demonstrated by shortness of breath MA 02115, USA. after moderate exertion and a rapid pulse on slight Accepted for publication 19 May 1987 effort. The men appeared well and there were no 306 Da Costa's syndrome or neurocirculatory asthenia 307 cardiac murmurs; however, sometimes the first heart ady common among soldiers". He wrote a report sound was diminished. Although there was about it to the War Department as early as Decem- improvement with several months of rest this did ber 1862 and finally summarised his thoughts in the not cure most of the cases. He considered that the 36 page article published in 1871 in the American process was attributable to the stress of the military Journal of Medical Sciences.4 campaigns with "great and prolonged exertion with Da Costa's clear description of this malady was the most unfavorable conditions possible-privation supplemented by several case histories. Although of rest, deficient food, bad water, and malaria." the story he tells related only to soldiers, he made the Four year later in February 1867, Dr W C point in the first paragraph that "Much ofwhat I am Maclean, who was Professor of Military Medicine at about to say I could duplicate from the experience of the British Army Medical School, wrote a lecture private practice." Therefore, this was not a phenom- entitled "Diseases of the heart in the British Army", enon seen solely in military surroundings. Later in which was published in the British Medical Jour- the article he confirmed this by mentioning that nal.3 His message regarding British soldiers was some of his patients had experienced typical symp- different from that of Hartshorne because he was toms before enlisting. After commenting that he had calling attention to cardiac hypertrophy and chosen the name of "irritable heart" for this "pecu- dilatation caused, he considered, by excessive exer- liar form of functional disorder", which he believed tion from carrying the soldier's field pack, which had also occurred in British troops earlier in the cen- amounted to over 60 pounds, and by the manner in tury, he made the following observations. which its straps constricted the circulation. No The condition often followed a period of hard ser- symptoms are described in Maclean's paper and it vice in the field or a febrile illness with or without hardly belongs in this historical sequence started by diarrhoea; less frequently it was seen after various Hartshorne, although both were concerned with the situations including battle wounds and scurvy. The role of physical exhaustion. main symptoms were palpitation with a rapid pulse, The first major publication on the topic was enti- with and without effort, and on occasion with slight tled "On irritable heart: a clinical study of a form of irregularities; chest pain near the cardiac apex either functional cardiac disorder and its consequences" by sharp and lancinating, or dull in character, coming Dr Jacob M Da Costa, published in the January with and without effort; and shortness of breath, 1871 issue of the American Journal of Medical Sci- again not necessarily associated with exertion. A ences.4 Da Costa was only one of a series of notable range of digestive complaints was also common. The physicians to be intrigued by this problem, which physical examination was described as not remark- over the next 70 years included some of the great able except for the unusually rapid pulse, a quick names in internal medicine. cardiac impulse, and sometimes apical systolic mur- Da Costa was born in 1833 on the Island of St murs. Treatment was prolonged and included rest Thomas in the West Indies. He was educated in and digitalis preparations, at times combined with Europe and came to Philadelphia in 1849, where at aconite or other drugs. A few patients could return the age of 16 he entered Jefferson Medical College. to full duty when they had completely recovered, He graduated three years later at 19 and went on to but most had to be assigned light duty or were enrich his education with 18 months of observation retired from the service. Da Costa made the point in the clinics of Paris and Vienna before returning to that one infrequent outcome was the development of practise in Philadelphia. Wooley reviewed his dis- cardiac hypertrophy, which he believed to have tinguished career,5 which included publication in developed in 28 of 200 cases seen. Finally, he cau- 1864, when Da Costa was only aged 31, of a volume tioned that such a condition occurs with "severe or on medical diagnosis which was so successful that it protracted" military campaigns, and he urged ade- ran to nine editions and was translated into German, quate physical training for new recruits, avoidance Russian, and French. Da Costa was appointed to the of forced marches, and provision for adequate con- position of Chairman of Medicine at Jefferson Med- valescence for those with acute infections before ical College, was elected President of the College of they returned to duty. Physicians of Philadelphia, and was selected as one Such were the features of Da Costa's syndrome as of the original members and later president of the set out in 1871. It must be borne in mind that on the Association of American Physicians. one hand, some of the patients indeed did have or Da Costa's role in military medicine came during had had malaria, typhoid, acute gastroenteritis, the Civil War when Philadelphia became the site of scurvy, malnutrition, and physical exhaustion, and several military hospitals. Da Costa was assigned to had a reason for temporary asthenia, and Da Costa one at a suburban Philadelphia estate on Turner's considered these in his description. And on the other Lane. Here Da Costa was exposed to a "cardiac mal- hand, a few others may have had organic heart dis- 308 Paul ease that was undiagnosable at the time, including a 700 bed hospital at Colchester in Essex. Other coronary or hypertensive heart disease, myocarditis, smaller rehabilitation centres were opened in other and myocardiopathy. Rheumatic and syphilitic heart areas in 1918. British physicians assigned at the out- disease would probably have been diagnosed. Dis- set to Hampstead included John Parkinson, J C counting these, there was left a vivid picture of a Meakins, and R M Wilson. residual group with Da Costa's "cardiac malady" Six physicians from the United States (Samuel A which is something else apart-an entity of uncer- Levine, Rufus A Morrison, Dr B S Oppenheimer, tain origin, consistent clinical features, and disabling Marcus A Rothschild, William St Lawrence, and but not life threatening consequences. Frank N Wilson) who were experienced in cardiol- Although the next major contributions in this area ogy were assigned in the summer of 1917 to Col- came during the first world war, there were minor chester by the Surgeon General of the United States evidences of interest from time to time in inter- Army on the advice of Dr Alfred E Cohn. Later, in vening years. The British authorities did alter the 1918, the Surgeon General set aside 200 beds at the weight and strappings ofthe soldiers' packs and later United States General Hospital No 9 at Lakewood, altered training drills in futile attempts to prevent New Jersey, for the same purpose. These were the problem from occurring in the troops. (Howell under the direction of Dr Francis W Peabody. On 6 has recently written an excellent review of the Brit- June 1918 the hospital was made a centre for cardio- ish military experience with this syndrome.6) The vascular disease. The medical officers there included condition is said to have been encountered during Harry D Clough, Cyrus C Sturgis, and Joseph T military operations in South Africa and India. Wearn. The first world war saw an amazing degree of con- One consequence of this heightened activity was a cern for the syndrome described by Da Costa. Some spate of new labels. Hartshorne had used the term of the best medical brains in Britain were recruited "muscular exhaustion of the heart" in 1864, Da to study the problem. The reason for the mobi- Costa had preferred "irritable heart" in 1871, Sir lisation of all this scientific talent was the extent of James Mackenzie used the label "general exhaus- Da Costa's syndrome in the allied military forces, tion" in 1916,11 Thomas Lewis used "effort syn- which became apparent during-the first months of drome" in his 1919 monograph,12 and the American the war. Alfred E Cohn wrote that as of 31 August workers preferred "neurocirculatory asthenia."'3 A 1918, 41 699 men had been discharged from the vague wastebasket term, "disordered action of the British Army because of heart disease, "most of heart", had also been used in the British Army, and them probably" because of Da Costa's syndrome.7 the equally unsatisfactory term "soldier's heart" was The German army seems to have had a similar used. In addition, the British army had the category experience. Goldscheider reported to the Medical "valvular disease of the heart", but in his series Society of Berlin in 1915 on the frequency in the Lewis reported that 161 of 277 patients with this troops of symptoms referable to the heart due to designation should be reclassified as "effort syn- muscular and nervous exhaustion.8 He cited no sta- drome."12 tistics. In 1916 Archives des Maladies du Coeur con- The most active and the earliest interest in Da tained a review of 23 published reports of cardiac Costa's syndrome during this period came from problems in wartime, many of which resembled Da British workers under Thomas Lewis who was the Costa's syndrome; 10 of the articles cited were Ger- newest bright star in the cardiac firmament and a man.9 remarkable investigator.14 Starting first at Univer- As early as 1915, the British Medical Research sity College Hospital in London and then at the mil- Committee had arranged for study of "disorders of itary hospitals in Hampstead and Colchester, Lewis the soldier's heart" under the general direction of and his team conducted a series of studies that Sir James Mackenzie at University College Hospital resulted in more than 20 published papers. in London. Later, an advisory committee was Sir Jamnes Mackenzie who was a leading member appointed including Mackenzie, Sir Clifford of this group summarised his views of the syndrome Allbutt, and Sir William Osler. Dr Thomas Lewis as seen in British soldiers in a report published in the was put in charge of the undertaking; and he, T F British Medical Journal in January 1916."1 He found Cotton, and F H Thiele made a brief report on the that a history of recent infections was present in problem in the British Medical Journal in November most cases, and emphasised that fatigue and exhaus- 1915.10 Early in 1916 the Director-General of the tion were always present, and breathlessness was Army Medical Service set aside the 250 bed Mount frequent. Depression and concern about heart dis- Vernon Hospital in Hampstead, London, for further ease was common, as were signs of vasomotor investigation and rehabilitative treatmnent ofthe con- instability of the hands. In a 1920 article in the same dition; late in 1917 the activities were transferred to journal, he wrote: "In a careful inquiry into the ori- Da Costa's syndrome or neurocirculatory asthenia 309 gin of ill health in over 2,000 soldiers I found that in changes in the PR intervals with and after effort.27 the case of about 80 per cent, the first onset of their Ninth, as described by Oppenheimer and illness began with some complaint of an infectious Rothschild, they may have represented two nature... In a number of cases there was no history populations-one with a positive family history and ofinfection, and the onset of the illness seemed to be a history of symptoms before enlistment and one due to a variety of circumstances ... want of rest had without such a background and with symptoms, evidently been the provoking agent in these particularly exhaustion and weakness, apparently instances."'5 precipitated by an event such as an acute infection.28 Another early publication from the group was that At Hampstead J C Meakins and R M Wilson of Parkinson,'4 who described in 1916 his experi- examined the reaction ofsoldiers with this syndrome ence with 90 "cardiac" cases passing through a casu- to a sudden visual stimulus followed by an alty clearing station in the British Expeditionary "unexpected discharge of a blank cartridge under Force in France in the period March 1915 to Jan- the examining couch".29 Subjects exposed to this uary 1916.16 He considered that 40 of these had singular ordeal developed more rapid respiratory "soldier's heart". Thirty nine ofthem complained of and pulse rates than did the normal soldiers. (It shortness of breath on exertion, 24 had precordial would not be surprising if other physiological and pain on effort (usually an ache that became sharper psychological effects resulted, but they were not with increased exertion), 16 stated they were easily described.) exhausted, and on auscultation nine had a short api- In February 1918 in the Lancet Lewis pointed to cal systolic murmur. After an average follow up of the screening and rehabilitative value of a graded seven months, only nine were back on full duty and recreation and exercise programme conducted in the 17 were on light duty. He suggested that the "rela- hospital.30 Of 558 men discharged over a six month tive cardiac inefficiency" must represent the effects period in 1916 (average follow up of 11 months) of previous infection, aging changes in men over 40, approximately half could be returned to some duty or a constitutional endowment of a heart "with lim- capacity. Such a successful programme sounded ited efficiency". remarkably easy to accept, especially for men com- A characteristic case cited was that of a 22 year old ing from the trenches. Cohn described how the pro- private. "Since age of 17, palpitation and shortness gramme included "setting up exercises, marches ofbreath on exertion. Light bench-work. September with the band; there were round games and tennis, 1914, enlisted. Same symptoms on doubling or hur- golf and cricket; athletic competitions, lectures and rying. September 1915 to France. Palpitation, short- picture shows... There were theatricals, often ness of breath, exhaustion and dull pain in fourth to arranged by the men themselves... And there was sixth left spaces about nipple line, all on marching. plenty of music; in one British camp there were two After one month admitted. Examination: no abnor- brass bands, an orchestra, a mandolin, and a banjo mal physical findings. Eight months later: full duty club."7 Lewis proposed that a systematic course of in France but no better." exercise be made available in all large military hospi- The group with Thomas Lewis reported other tals, a recommendation strongly endorsed by Sir observations on these soldiers. Firstly, with test William Osler3' and Sir James Mackenzie." exercise they became more symptomatic than con- Lewis summarised his experience in a 144 page trol subjects; they were able to do less physically monograph published in 1919 entitled "The sol- than the controls, and their pulse rates and systolic dier's heart and the effort syndrome".'2 He con- pressures rose more than those ofthe presumed nor- sidered that such a rubric encompassed six mal soldiers.'7 Second, there was no appreciable subgroups-those with a constitutional nervous or cardiac enlargement on orthodiographic mea- physical weakness, some exposed to extraordinarily surement.'8 Third, they seemed to have a slightly unfavourable conditions of work and sleep, those reduced vital capacity.'9 Fourth, the men might convalescent from acute infectious illnesses, a few show hyperalgesia in the precordial area.20 Fifth, with as yet unrecognised infection, a small group although in 1916 they reported that the "cause of recovering from gas poisoning, and another small breathlessness is absence of an adequate supply of group with unrecognised heart disease. He consid- buffer salts in the blood,"'" a later (1919) study ered it not remarkable that some men developed showed no clear reduction in the alkaline reserve of symptoms under wartime stresses, and pointed out the blood.22 Sixth, symptoms were not improved by that the syndrome was also found in civilian life. He the administration of digitalis.23 Seventh, when emphasised the universality of the symptom breath- given atropine, pilocarpine, and amyl nitrite they lessness (only rarely found at rest), which he consid- did not behave very differently from the control ered was probably related to acid-base alterations in group.2426 Eighth, they did not develop distinctive the blood. Fatigue, he noted, was also universal as a 310 Paul complaint and half of the patients had vague left was greater in the patients than in the control sub- chest distress with or after effort, with at times jects.34 Adams and Sturgis found little evidence of a hyperaesthesia of the skin or muscles of the chest reduced vital capacity in the men,35 nor could they wall. Palpitation was also very frequent, and there confirm the 1916 view of Lewis and his colleagues21 was occasional fainting and some giddiness. He did of any abnormality in the carbon dioxide combining not agree with Hartshorne and Maclean that this capacity of the blood and in acid-base balance. syndrome represented heart strain. He did not find A comprehensive report from the American side that consumption of alcohol or tobacco, or the pres- was prepared in 1919 by Dr Alfred Cohn of ence of hyperthyroidism, were aetiological factors Rockefeller University, based both on his clinical (patients with effort syndrome used less tobacco and experience in England at the Military Hospital at alcohol than soldiers with gunshot wounds), nor did Colchester and in the hospitals of the American he find evidence for a primary defect of the nervous Expeditionary Force.7 He reasoned that "the heart system. He concluded that the dominant aetiological in convalescence after acute infectious disease and factor in the clinical histories of soldiers com- the Irritable Heart are probably not the same thing" plaining of the "effort syndrome" was "infection of and vigorously proposed that "this symptom com- one kind or another". In his emphasis on the role of plex is neurotic". He minimised but did not discard infection, he agreed with Sir James Mackenzie. He the importance of constitutional inferiority, writing encouraged the use of a hygienic regimen including that "taking constitutional predisposition into outdoor activities, and of reassurance, and empha- account is essential, but as a complete account of sised that bed rest was harmful. failure, it appears to be inadequate." He ended his After the armistice in 1918, Lewis assisted the paper with the conviction that "the disorder is British Ministry of Pensions in its assessment of essentially a neurosis, depending upon anxiety and cases of cardiovascular disability. An outpatient fear; that it is removed by the disappearance of the clinic was established at University College Hospital inciting cause and that it is cured by measures in London, and Parkinson was placed in charge of designed to influence the neurotic state." beds for convalescent cases at the Ministry of Pen- Neuhof, also writing in 1919 on the topic "The sions hospital at Orpington. (Brief summaries of the Irritable Heart in General Practice," believed that contributions of Lewis and his group during and "the soldier's irritable heart is no new complex, but immediately after the first world war may be found is the same syndrome seen in civil life, intensified in the annual reports of the Medical Research Com- and multiplied by training and war conditions."36 mittee, 1914-1915 to 1919-1920, published in Lon- He believed that "some great emotion, fright, dread, don by His Majesty's Stationery Office.) shock, is usually the directly antecedent cause of the In 1925 Dr Ronald T Grant, who was associated outbreak of the cardiac symptoms. Reflex excitation with Lewis, published a five year follow-up of 665 from the gastrointestinal tract is the next most fre- cases of "effort syndrome" seen at the Hampstead quent." The fundamental process in his view was and Colchester Military Heart Hospitals during the "hyperexcitation of the sympathetic nervous sys- years 1916-18 and who subsequently lived in the tem". London area.32 He traced over 90% of the men. Dr Paul Dudley White of Boston had received a Only 15% seemed to have recovered completely but letter from Dr Alfred Cohn dated 17 May 1917 sug- the overall death rate in the group was not remark- gesting that he become a member of the American able, although many of the men had developed pul- contingent destined to go to England to work under monary tuberculosis. He reasoned that incipient Thomas Lewis at Hampstead and Colchester. Paul cardiac disease was not a factor in the syndrome. White, having been trained by Lewis, was clearly Meanwhile, on the other side of the Atlantic in interested in the proposal but found that he, as a Lakewood, New Jersey, at the United States Army member of the United States Army Medical Corps General Hospital No 9, a more modest wartime Reserve, would not be released from his commit- investigative effort was initiated. Dr Francis Pea- ments to the Massachusetts General Base Hospital body with Dr Clough, Dr Sturgis, Dr Wearn, and No 6. Indeed he was placed on active military ser- Dr Tompkins reported that 65 soldiers with the vice on 24 May 1917, only seven days after the date "constitutionally inferior" type of the syndrome of Cohn's letter soliciting his participation. Paul showed an abnormal rise in systolic blood pressure White had visited the Hampstead Military Hospital or pulse rate or both in response to an intramuscular on 29 August 1916 and was familiar with British injection of adrenaline.33 The same group without interest in the subject. Peabody and Clough also administered an injection Paul White's first publication in this area came of atropine to these soldiers and noted that the after the war in 1920 when he pointed out that, since rebound increase in pulse rate after an initial slowing returning to civilian life, he had seen in six or eight Da Costa's syndrome or neurocirculatory asthenia 311 weeks 12 young patients with "effort syndrome".37 neurocirculatory asthenia were considered not to be This was the first scientific paper to emphasise how identical with those of fear alone. common this problem was in civilian practice, and it In 1958, Kannel et al reviewed the resting electro- was succeeded in 1934 by a more comprehensive cardiogram of 203 individuals in the Framingham discussion. 13 Most ofhis patients were women, their study considered to have neurocirculatory asthenia symptoms were typical, there was no evidence of and concluded that no electrocardiographic abnor- organic heart disease, and he underscored the malities were characteristic of this syndrome,40 a importance of correct diagnosis to avoid unneces- finding also reported by others. sary invalidism. He did not support the views of Paul White and his group concluded that the Lewis and Mackenzie of an infectious or bacterial cause of the condition was unknown and that simple toxic aetiology for most cases. Here at last was an reassurance and observation over time were the most opportunity to consider the syndrome away from the effective therapeutic measures. In their last publica- unusual and often highly unfavourable conditions of tion in 1972, Cohen and White additionally sug- wartime with their prevalence of respiratory and gested that the syndrome might present in two other infections, abnormal living conditions, uncer- forms-a mild disorder called neurocirculatory tain diets, and fear of imminent death. Subsequently asthenia, and a severe illness that was actually manic over the next 30 years he and his associates depressive disease presenting at time with cardio- (especially Mandel E Cohen, and others including vascular, respiratory, and fatigue symptoms in addi- Edwin 0 Wheeler, Henry B Craig, William P Chap- tion to other complaints.41 man, Stanley Cobb, Jacques Carlotti, and Eleanor These extensive long term studies carried out W Reed) produced a series of reports that explored under both peacetime and wartime (second world many facets of this puzzling condition. They used war) conditions in civilian and military populations the term "neurocirculatory asthenia", which had give valuable information on many aspects of the been preferred by the United States investigators at problem. Most important of all, they drew attention the end of the first world war. to neurocirculatory asthenia in the daily practice of Cohen and White reported that 2-4% of the pop- cardiology. ulation had this disorder. The mean age of onset was In the midst of these investigations by Paul about 25 years.38 The disorder affected twice as White's laboratory, a major report on the syndrome many women as men, often occurring in successive was presented by Paul Wood in his three generations in the same family. Unlike most earlier Goulstonian Lectures given to the Royal College of investigators they called attention to the chronic Physicians in London in 1941 during the second presence of sighing respirations, the complaint of world war.42 Paul Wood flatly stated that he no smothering sensations (especially in crowds), and to longer considered that the cause and mechanism the sign of a flushed face and neck; as well as to brisk were unknown. His was an extensive review of pub- patellar and Achilles deep tendon reflexes. In a 20 lished reports with observations of his own. In his year follow up of 173 patients, over 70% continued study of200 military cases, the symptoms in order of to have some symptoms, but only 15% had frequency were breathlessness (93%), palpitation important disability. Symptoms tended to increase (89%), fatigue (88%), sweats (80%), nervousness with muscular effort, unusual emotion-provoking (80%), dizziness (78%), and left chest pain (78%). situations, disagreeable thoughts, and exposure to Only 24% of the subjects could hold their breaths crowds, but two thirds of the patients could identify for 30 seconds or more, sweat was visible on the no stimulus. Painful stimuli such as heat and a tight palms in 67%, and 48% appeared nervous. He con- sphygmomanometer cuff produced abnormal sidered that the left chest pain might have several responses in subjects with neurocirculatory asthenia explanations including a functional disturbance of but not in controls. Patients could not continue as the respiratory muscles, strain of the thoracic mus- long as control subjects with moderate muscular cles, or "minimum trauma from the overacting heart effort, including running on a treadmill or stepping of cardiac neurosis." He also commented on raised up and down. They also showed higher pulse and resting heart rates, sweating of the palms, soles, and respiratory rates and blood lactate concentrations axillae, and hyperventilation after forced breathing with exercise than the controls, and pulmonary ven- (but he did not believe that hyperventilation was tilation was higher but oxygen consumption was the responsible for the symptoms and signs). He consid- same. These observations coincided with those of ered that Da Costa's syndrome should be regarded the British workers Jones and Scarisbrick, published "as an emotional reactive pattern peculiar to psycho- in 1946.39 Rebreathing a mixture containing pathic personalities and to subjects of almost any increased amounts of carbon dioxide often form of psychoneurosis." reproduced the symptoms. The symptoms of Paul Wood's conclusions included the following: 312 Paul "The symptoms and signs of Da Costa's syn- exploration. The first of these has been the sug- drome more closely resemble those of emotion, gestion by some that there is an overlap between especially fear, than those of effort in the normal neurocirculatory asthenia and mitral valve prolapse, subject. The mechanism of somatic manifestations and that both can be considered within a single depends on central stimulation, not upon hyper- rubric. sensitivity of the peripheral autonomic 'gear'. This Jeresaty wrote in 1979 that "many of the patients central stimulus is emotional, and is commonly the previously described as suffering from Da Costa's result of fear. The reaction becomes linked to effort syndrome, soldier's heart, the effort syndrome, and by a variety of devices, which include misinter- neurocirculatory asthenia would now be classified pretation of emotional symptoms, certain vicious under the heading of mitral valve prolapse syn- circular patterns, the growth of a conviction that the drome".46 Barlow and Pocock stated in 1984: "We heart is to blame, consequent fear of sudden death are also aware that some patients diagnosed by us as on exertion, conditioning and hysteria. Incapacity primary mitral valve prolapse syndrome would be tends to be exaggerated consciously or subcon- classified by others as neurocirculatory asthenia, Da sciously in order to protect the individual from fur- Costa's syndrome, non-specific T-wave changes, ther painful emotional experience." atypical chest pain syndrome, so-called 'syndrome Thus Paul Wood, after wartime experience with X' or similar conditions".47 It is important that Bar- the condition, came down squarely on the side of low and Pocock spoke only of "some patients". viewing Da Costa's syndrome as a manifestation of Wooley noted in 1985 and also earlier how "As emotion, more in keeping with the view of Cohn knowledge and technology progressed, the pathway than that of Mackenzie or Lewis, and unlike that of from neurocirculatory asthenia would eventually White and Cohen, who considered that the issue was lead to anxiety neuroses of World War II, systolic decidedly more complex. click and late systolic murmur syndrome of the It was doubtless in part because of Paul Wood's 1960's, and the mitral valve prolapse syndrome, influential views, well spread over three issues of the panic disorders, and autonomic dysfunction states of British Medical Journal in 1941, that during the sec- the 1970's and 1980's".48 ond world war there was a diminished interest in Da The fact that the disorders referred to all share Costa's syndrome as a medical entity. Many of the uncertain aetiology, vague symptoms, no means of cases seem to have been treated by psychiatrists and specific identification by laboratory means, and are ended up with various diagnostic labels. In the third usually unresponsive to conventional treatment edition ofhis textbook on heart disease, published in should not in itself justify creating a new umbrella 1968, Paul Wood restated his views in accord with label. Because both mitral valve prolapse and neuro- this impression: circulatory asthenia are common some individuals "It should be understood that there is no essential are likely to show evidence of both conditions. difference between 'effort syndrome' and 'cardiac It is important to emphasise, as have nearly all of neurosis', they are merely clothed differently, the those physicians who studied the problem carefully, former in battle dress, and latter in nylon. In civil that all patients with neurocirculatory asthenia com- life the condition accounts for 10 to 15 per cent of all plain of undue shortness of breath on effort and cases referred to cardiovascular clinics; it is common often at rest, approximately 90% have palpitation in children, and occurs more often in women than in and fatigue, and approximately 50-75% report chest men, the ratio being 3:2. It has a preference for the pain. This is not what has usually been reported emotional races, especially the Jews and Italians. In with the mitral valve prolapse syndrome. It is the first world war there were some 60,000 'effort apparent that most young patients with mitral valve syndrome' casualties in the British forces; in the sec- prolapse syndrome have no symptoms at all if the ond a more enlighted view was taken, the majority of condition is detected on a screening examination; these cases receiving appropriate psychiatric labels and even among those seen in the usual clinic (office) and management."43 setting, which concentrates those patients with Friedberg, in the third edition of his text Diseases symptoms, symptoms are much less common than in of the Heart, published in 1966, also expressed a neurocirculatory asthenia. Jeresaty reported chest psychiatrically oriented view when he wrote: "The pain in 61%, fatigue in 42%, and dyspnoea in only underlying cause appears to be a fundamental ego 38% of 100 cases of mitral valve prolapse.46 Barlow insecurity arising from psychological problems et al in their original 1968 description of 63 patients which began in infancy and childhood".44 A more with systolic murmurs and in some cases non- recent (1974) review by Caranasos expresses a simi- ejection clicks, also described tiredness, palpitation, lar sentiment.45 breathlessness, or chest pain in only 39 (62%).49 The past few years have seen two further lines of Leatham and Brigden wrote firmly in 1980 in an Da Costa's syndrome or neurocirculatory asthenia 313 article entitled "Mild Mitral Regurgitation and the tal in Jerusalem treated five men and five women Mitral Prolapse Fiasco" that "isolated disease of the with neurocirculatory asthenia with intravenous mitral valve causing mild or moderate reflux seldom propranolol. In all of them there was improvement causes symptoms other than those of iatrogenic anx- in ST-T abnormalities in the resting electro- iety."50 Leor and Markiewicz from the Rambam cardiograms.58 Here again, no definite conclusions Medical Center in Haifa, Israel, used auscultation can be drawn from such observations. Indeed, the and echocardiography to study 42 young soldiers whole area of the treatment of disorders associated with neurocirculatory asthenia; they concluded that with anxiety with ,B blocking drugs appears contro- "mitral prolapse and neurocirculatory asthenia do versial.59 not appear to be related".51 Silverman etal studied Da Costa's syndrome or neurocirculatory asthenia 68 patients seen in private practice, 57 ofwhom were has been a common condition in the experience of women, in whom mitral valve prolapse was diag- many seasoned clinicians. Past studies have shown nosed by echocardiography.52 While they concluded that it has often had a familial background, has that the symptoms ofneurocirculatory asthenia were occurred in both civilian and military life, and more common in patients with mitral valve prolapse especially in women, has had certain identifiable than in an age and sex matched control population, symptoms, no specific signs, and few demonstrable only 34 of the 68 complained of dyspnoea (as did 19 physiological and psychological abnormalities. of the controls) and fatigue. Symptoms related to There has been no, or a poor, therapeutic response effort were not mentioned. Retchin et al investigated to rest, and no convincing evidence of benefit from 274 outpatients and suggested that "symptoms and diet, surgery (adrenal gland denervation was prac- dysfunction are not related to the presence of mitral tised by Crile in the 1930s6 61), or drugs. A pro- valve prolapse by echocardiography".53 Devereux gramme of reassurance, exercise, and physical et al in another large study concluded that "non- fitness has been of value. anginal chest pain, dyspnoea, panic attacks and elec- It is important to be able to recognise the condi- trocardiographic abnormalities have appeared to be tion irrespective of the label used. The diagnosis is associated with mitral valve prolapse because of usually not difficult for an interested reasonably ascertainment bias and an erroneous classification of intelligent physician. Be alert for the younger differences between men and women as being due to patient with unexplained shortness of breath, easy mitral valve prolapse".54 fatigue, and a history of palpitation and atypical It seems best to keep neurocirculatory asthenia chest pain, who sighs frequently during the course and mitral valve prolapse as separate categories for of the conversation. All too many patients with this the time being because they do not have sufficient syndrome, mainly women, are still mistakenly similarities to justify a single label. This does not labelled as having organic heart disease including mean that a few individuals do not demonstrate evi- angina pectoris, and this leads to the additional dence of both conditions. The hyperkinetic heart problem of an unnecessary cardiac neurosis. (Not all syndrome also appears to be different from neuro- patients with neurocirculatory asthenia have a circulatory asthenia and should also be considered as cardiac neurosis and not all patients with a cardiac a separate entity." 16 neurosis have neurocirculatory asthenia.) It is essen- The second line of investigation has been the tial to be able to reassure the patient with treatment of neurocirculatory asthenia with j block- neurocirculatory asthenia, to understand that the ing agents. Here, much as in the mitral valve pro- condition may be life long with remissions and lapse story, there has been a modest amount of exacerbations, and to appreciate that it may to some smoke but not much fire. Caranasos in 1974 sum- extent limit physically strenuous effort. Finally, it marised the situation as follows: "Recently pro- does not appear profitable at this time to attempt to pranolol has been found effective in diminishing or combine neurocirculatory asthenia and mitral valve even abolishing the cardiovascular signs and symp- prolapse within a single diagnostic category. toms of 'NCA', but the psychic symptoms are unaffected".45 Rimon et al in an unimpressive, References uncontrolled study published in 1979 in the Israel 1 Hartshorne H. On heart disease in the army. Am J Med Annals of Psychiatry, listed many rion-specific Sci 1864;48:89-92. symptoms such as depression, palpitation, difficulty 2 Stille A. 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